Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

L.C. Tsoi; P.E. Stuart; C. Tian; J.E. Gudjonsson; S. Das; M. Zawistowski; E. Ellinghaus; J.N. Barker; V. Chandran; N. Dand; K.C. Duffin; C. Enerbäck; T. Esko; A. Franke; D.D. Gladman; P. Hoffmann; K. Kingo; S. Kõks; G.G. Krueger; H.W. Lim; A. Metspalu; U. Mrowietz; S. Mucha; P. Rahman; A. Reis; T. Tejasvi; R. Trembath; J.J. Voorhees; S. Weidinger; M. Weichenthal; X. Wen; N. Eriksson; H.M. Kang; D.A. Hinds; R.P. Nair; G.R. Abecasis; J.T. Elder

doi:10.1038/ncomms15382

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Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

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Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

L.C. Tsoi, P.E. Stuart, C. Tian, J.E. Gudjonsson, S. Das, M. Zawistowski, E. Ellinghaus, J.N. Barker, V. Chandran, N. Dand, …

Nature Communications, Vol.8(1)

2017

DOI: https://doi.org/10.1038/ncomms15382

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Abstract

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10−89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.

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Title: Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants
Authors/Creators: L.C. Tsoi (Author/Creator) - University of Michigan
P.E. Stuart (Author/Creator) - University of Michigan
C. Tian (Author/Creator) - 23andMe Inc.
J.E. Gudjonsson (Author/Creator) - University of Michigan
S. Das (Author/Creator) - University of Michigan
M. Zawistowski (Author/Creator) - University of Michigan
E. Ellinghaus (Author/Creator) - Christian-Albrechts-Universität zu Kiel
J.N. Barker (Author/Creator) - King's College London
V. Chandran (Author/Creator) - University of Toronto
N. Dand (Author/Creator) - King's College London
K.C. Duffin (Author/Creator) - University of Utah
C. Enerbäck (Author/Creator) - Linköping University
T. Esko (Author/Creator) - University of Tartu
A. Franke (Author/Creator) - Christian-Albrechts-Universität zu Kiel
D.D. Gladman (Author/Creator) - University of Toronto
P. Hoffmann (Author/Creator) - University of Basel
K. Kingo (Author/Creator) - Tartu University Hospital
S. Kõks (Author/Creator) - Estonian University of Life Sciences
G.G. Krueger (Author/Creator) - University of Utah
H.W. Lim (Author/Creator) - Henry Ford Hospital
A. Metspalu (Author/Creator) - University of Tartu
U. Mrowietz (Author/Creator) - Christian-Albrechts-Universität zu Kiel
S. Mucha (Author/Creator) - Christian-Albrechts-Universität zu Kiel
P. Rahman (Author/Creator) - Memorial University of Newfoundland
A. Reis (Author/Creator) - Friedrich-Alexander-Universität Erlangen-Nürnberg
T. Tejasvi (Author/Creator) - University of Michigan
R. Trembath (Author/Creator) - King's College London
J.J. Voorhees (Author/Creator) - University of Michigan
S. Weidinger (Author/Creator) - Christian-Albrechts-Universität zu Kiel
M. Weichenthal (Author/Creator) - Christian-Albrechts-Universität zu Kiel
X. Wen (Author/Creator) - University of Michigan
N. Eriksson (Author/Creator) - 23andMe Inc.
H.M. Kang (Author/Creator) - University of Michigan
D.A. Hinds (Author/Creator) - 23andMe Inc.
R.P. Nair (Author/Creator) - University of Michigan
G.R. Abecasis (Author/Creator) - University of Michigan
J.T. Elder (Author/Creator) - Veterans Health Administration
Publication Details: Nature Communications, Vol.8(1)
Publisher: Springer Nature
Identifiers: 991005544407207891
Copyright: © 2019 Springer Nature Limited
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.106 Rheumatology; 1.106.737 Psoriasis
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics